DNCB-induced AD-like Lesions Research Articles

Oleanolic Acid Alleviates Atopic Dermatitis-like Responses In Vivo and In Vitro.

Oleanolic acid (OA) is a pentacyclic triterpenoid, abundantly found in plants of the Oleaceae family, and is well known for its beneficial pharmacological activities. Previously, we reported the inhibitory effect of OA on mast cell-mediated allergic inflammation. In this study, we investigated the effects of OA on atopic dermatitis (AD)-like skin lesions and its underlying mechanism of action. We evaluated the inhibitory effect of OA on AD-like responses and the possible mechanisms using a 1-chloro-2,4-dinitrochlorobenzene (DNCB)-induced AD animal model and tumor necrosis factor (TNF)-α/interferon (IFN)-γ-stimulated HaCaT keratinocytes. We found that OA has anti-atopic effects, including histological alterations, on DNCB-induced AD-like lesions in mice. Moreover, it suppressed the expression of Th2 type cytokines and chemokines in the AD mouse model and TNF-α/IFN-γ-induced HaCaT keratinocytes by blocking the activation of serine-threonine kinase Akt, nuclear factor-κB, and the signal transducer and activator of transcription 1. The results demonstrate that OA inhibits AD-like symptoms and regulates the inflammatory mediators; therefore, it may be used as an effective and attractive therapeutic agent for allergic disorders, such as AD. Moreover, the findings of this study provide novel insights into the potential pharmacological targets of OA for treating AD.

Topical Spilanthol Inhibits MAPK Signaling and Ameliorates Allergic Inflammation in DNCB-Induced Atopic Dermatitis in Mice.

Atopic dermatitis (AD) is a recurrent allergic skin disease caused by genetic and environmental factors. Patients with AD may experience immune imbalance, increased levels of mast cells, immunoglobulin (Ig) E and pro-inflammatory factors (Cyclooxygenase, COX-2 and inducible NO synthase, iNOS). While spilanthol (SP) has anti-inflammatory and analgesic activities, its effect on AD remains to be explored. To develop a new means of SP, inflammation-related symptoms of AD were alleviated, and 2,4-dinitrochlorobenzene (DNCB) was used to induce AD-like skin lesions in BALB/c mice. Histopathological analysis was used to examine mast cells and eosinophils infiltration in AD-like skin lesions. The levels of IgE, IgG1 and IgG2a were measured by enzyme-linked immunosorbent assay (ELISA) kits. Western blot was used for analysis of the mitogen-activated protein kinase (MAPK) pathways and COX-2 and iNOS protein expression. Topical SP treatment reduced serum IgE and IgG2a levels and suppressed COX-2 and iNOS expression via blocked mitogen-activated protein kinase (MAPK) pathways in DNCB-induced AD-like lesions. Histopathological examination revealed that SP reduced epidermal thickness and collagen accumulation and inhibited mast cells and eosinophils infiltration into the AD-like lesions skin. These results indicate that SP may protect against AD skin lesions through inhibited MAPK signaling pathways and may diminish the infiltration of inflammatory cells to block allergic inflammation.

Therapeutic potential of topically administered γ-AlOOH on 2,4-dinitrochlorobenzene-induced atopic dermatitis-like lesions in Balb/c mice.

Boehmite (γ-AlOOH) has a wide range of applications in a variety of industrial and biological fields. However, little is known about its potential roles in skin diseases. The current study investigated its effect on atopic dermatitis (AD). Following characterization, cytotoxicity, pro-inflammatory response and oxidative stress associated with boehmite were assessed, using TNF-α-induced keratinocytes and mast cells. In addition, therapeutic effects of boehmite, topically administered to Balb/c mice induced by 2,4-dinitrochlorobenzene (DNCB), were evaluated. Expression of cytokines (TLSP, IL-25 and IL-33) and the generation of ROS from keratinocytes induced by TNF-α were significantly inhibited by boehmite without affecting cell viability. MAPKs (ERK, JNK and p38) required for cytokine expression were suppressed by boehmite treatment. Up-regulation of cytokines (TSLP, IL-4, IL-5, IL-13, RANTES) in human mast cells treated with phorbol 12-myristate 13-acetate and calcium ionophore was also suppressed by boehmite. Boehmite improved the AD severity score, epidermal hyperplasia and transepidermal water loss in DNCB-induced AD-like lesions. Moreover, Th2-mediated cytokine expression, mast cell hyperplasia and destruction of the skin barrier were improved by boehmite treatment. Overall, we demonstrated that boehmite may potentially protect against AD.

Protective effect of polysaccharide nucleic acid fraction of bacillus Calmette-Guerin against atopic dermatitis in Nc/Nga mice

Objective To evaluate the protective effect of polysaccharide nucleic acid fraction of bacillus Calmette-Guerin (BCG-PSN) against atopic dermatitis (AD) in Nc/Nga mice, and to explore its possible mechanism. Methods Sixteen Nc/Nga mice were classified into normal control group (n = 4) , low-concentration BCG-PSN group (n=5) and high-concentration BCG-PSN group (n=7) to be subcutaneously injected with sodium chloride physiological solution, BCG-PSN of 0.1 mg/kg and 0.5 mg/kg respectively, at 1, 8, 15 and 22 days of age. Dinitrochlorobenzene (DNCB) was repeatedly and topically applied to these Nc/Nga mice to induce AD-like lesions at 49 days of age. The preventive effect of BCG-PSN against AD was evaluated by dermatitis scores, scratching frequency, histopathological manifestations and immunological parameters (including IgE, interleukin (IL) -4 and -12, and interferon (IFN) -γ) . Results Repeated injection of BCG-PSN within 4 weeks after birth significantly decreased the severity of DNCB-induced AD-like lesions, dermatitis scores and scratching behavior in Nc/Nga mice. There was no statistical difference in scratching frequency between the high- and low-concentration BCG-PSN groups. BCG-PSN treatment reduced the plasma level of IgE in Nc/Nga mice in a dose-dependent manner. BCG-PSN at 0.5 mg/kg increased the number of cells secreting IFN-γ in skin lesions of mice. Both doses of BCG-PSN down-regulated IL-4 level, but up-regulated IL-12 level in the culture supernatant of spleen mononuclear cells from mice. Conclusion Early injection of BCG-PSN could protect Nc/Nga mice against dermatitis by promoting the proliferation of IFN-γ-secreting cells, increasing the synthesis of IL-12, and reducing the levels of IL-4 and IgE. Key words: Dermatitis, atopic; Mice, Nc/Nga; Dendritic cells; BCG-PSN